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Analysis On Matrine Toxicity And HPLC Determination Of Matrine In Sheep Plasma

Posted on:2016-06-10Degree:MasterType:Thesis
Country:ChinaCandidate:L Y YangFull Text:PDF
GTID:2283330464463973Subject:Clinical Veterinary Medicine
Abstract/Summary:PDF Full Text Request
The main objective of this paper was to analyze on the toxicology of Matrine, which is the active ingredient of Sophora alopecuroides, and the absaptive effects of Matrine administrave through sheep skin. Sophora alopecuroides used in this paper was collected from Erdos Otog front Banner, and the Matrine samples were obtained through chemical purification by Academy of Agricultural Sciences Inner Mongolia Veterinary Research Institute.Experiment 1 is Matrine toxicity test:certain concentration of Matrine solution was used to feed mice, the symptoms of acute toxicity in mice were recorded, the main target organ aimed by Matrine was explored, the half lethal dose of Matrine on mice was detected and the degree of recovery of target organ after stopping intragastric administration of Matrine was observed. The median lethal dose of Matrine on mice was calculated according to the Bliss formula. Results showed as follows:through the comparison of observation and histopathology, it has been found that the target organs aimed by Matrine are lung, liver, brain, kidney and heart. The degree of recovery for the lung is worse, for which the brain, liver and kidney were better.Experiment 2 is irritant experiment including skin irritation and eye irritation. The the skin irritation test includes single skin irritation tests and multiple skin irritation tests, in which two fomat of drugs were used:matrine and matrine transdermal formulation. Transdermal enhancers(azone and propylene glycol) are added into the Matrine of skin preparation group, the tested animals are rabbits. The results showed as follows:the single and multiple stimulation group had no irritation to the skin and conjunctiva without matrine group transdennal agent; while the addition of transdermal enhancers in the transdenmal preparation of matrine of the single and multiple stimulation group showed moderate irritation to the skin. The main observations were the rubedo eyelids, the thickened skin, the seabed skin, the falling-off crusts and the new generating skin; the pathological characteristics showed the hyperplasiaing and falling off of the stratum corneum of the skin, the edema and fracture of dermal fiber, the congertion and hemorrhage of stimulated small vessel, and the infiltration of inflammatory cell. Experiment 3 is Matrine liquid petrographic study:, HPLC assay was established for detecting matrine in the plasma using SHIMADZU LC-2010C liquid chromatography, of which sophoridine was used as the internal standard. Methanol was used as precipitating protein in the plasma pretreatment step, it was detected by UV detector at the wavelength of 220nm, and the mobile phase were A[0.05moL/L potassium dihydrogen phosphate (the pH value of dipotassium hydrogen phosphate was 6.46)] and B[methanol (A/B,65:35)], which were used for elute at the same concentration by the flow rate of 0.8mL·min-1. At last a high performance liquid in sheep plasma detection of matrine alkaloid chromatography was established, chromatographic peak showed a pleasant result. The linear relationship of matrine showed R2>0.999. A non meridian tube model was used for the MT to calculate the pharmacokinetic parameters of efficacy. The experiment proved that the main function parts of topical Matrine was body surface, only minimal drugs through adding transdermal enhancers could enter the systemic circulation, which proved that the absorption amout of Matrine to the blood through the skin was minimal. A method for detecting Matrine alkaloids in sheep plasma was established in this experiment.
Keywords/Search Tags:Matrine, Skin Irritation, Conjunctival Irritation, Internal Standard, Blood Drug Concentration, Pharmacokinetics
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